Acids and Alkalis Caustic Agents

Acids and Alkalis Corrosives - denotes an acidic substance Caustics - denotes an alkaline substance Federal Hazardous Substance Act of 1967 Cause tissue injury by a chemical reaction - accept (base) or donate (acid) a proton. Severity of tissue injury is determined by: the substances pH or pKa, concentration, duration of contact and volume of contact.

Acids and Alkalis Ingestion is an extremely common event, accounts 229,500 alkali drain cleaners and acidic toilet bowl cleaners are responsible for most fatalities 10% of caustic ingestions result in severe injury requiring treatment between 1-2% result in stricture formation 80% of ingestions are in children > 5 years most adult ingestions are intentional

Acids Mechanism of action - denature proteins coagulative necrosis cell morphology not grossly altered, destruction of enzymatic proteins acid burns cause formation of tough leathery eschar or coagulum (which sloughs in 3-4 days) little to no systemic absorption stomach is most commonly involved organ

Acids, cont. Management - any ingestion constitutes a medical emergency skin or eye contact - flush with copious amounts of water. remove contact lens and jewelry wash skin with mild soap do not apply topical ointments, creams, or dressings

Acids, cont. Ingestion serious solid ingestions are rare as the particles usually stick to the oropharynx, but liquid exposures can be severe burning is so severe patient probably can not swallow do not give carbonated beverages do not give water, water + acid explosive release of steam - exothermic reaction do not induce vomiting maintain airway

Acids, cont. Clinical concerns: perforation may occur after the third to fourth day as eschar sloughs gastric outlet obstruction may develop over a 2-4 week period upper GIT hemorrhage

Acids, cont. Common acid containing sources toilet bowl cleaners automotive batteries rust removal porducts metal cleaning products drain cleaning products

Acids, cont. Boric acid - H3BO3 weak bacteriostatic agent used as an insecticide for roaches (roach motels) do not apply to open wounds toxic to the kidneys can cause a severe dermatitis - boiled lobster rash - seen on palmar and plantar surfaces and buttocks

Acids, cont. Carbolic acid - phenol one of the oldest disinfectants known used as a deodorizer - Lysol absorbed through intact skin Signs - nausea, diaphoresis, CNS stimulation, hypotension, renal failure Treatment - demulcents, activated charcoal

Alkalis More common cause of toxicity than acids Most common alkaline agents causing toxicity Ammonia Sodium hydroxide both of these are found in household cleaners and drain cleaners Most cases are in children under the age of five years

Alkalis, cont. Mechanism of action tissue injury causes by liquefactive necrosis (saponification of fats and solubilization of proteins) cell death occurs from emulsification and disruption of cell membranes OH ion reacts with tissue collagen causing it to swell and shorten most severe injured tissues are the squamous epithelial cells of the oropharynx and esophagus (the most commonly involved organ) alkali burns to the skin are yellow, soapy and soft

Acids, cont. Clinical concerns tissue edema - leading to possible airway obstruction erythema ulceration necrosis of tissues with possible stricture formation (depends on depth of burn) perforation can occur

Alkalis, cont. Management of toxicity eye and skin contamination - flush with copious amounts of water ingestion - any ingestion constitutes a medical emergency do not induce vomiting give demulcents (milk, water or egg whites)

Alkalis, cont. Common base containing sources drain cleaning products ammonia - containing products over cleaning products swimming pool cleaning products automatic dishwasher detergent hair relaxers clinitest tablets bleaches cement

Alkalis, cont. Disc batteries Soaps - most are non toxic usually pass through GIT in 48 hours can become lodged pressure necrosis leak out potassium or sodium hydroxide Soaps - most are non toxic have emetic action so vomiting is spontaneous automatic dishwashing soap - highly corrosive

Alkalis, cont. Ammonia - NH3 - at room temp is a highly H2O soluble, colorless, irritant gas with a pungent odor. 1993 anhydrous ammonia was the 3rd most produced chemical in the US farmers use 1/3 for fertilizer and animal feed A component of may household cleaning products - glass cleaners, toilet bowl cleaners, metal polishes, etc.) highly alkaline and corrosive household ammonia - not as corrosive

Alkalis, cont. Most common mechanism is exposure to anhydrous ammonia - liquid or gas NH3 + H2O ------ NH4OH this reaction is exothermic - causes significant thermal injury Ammonium hydroxide also causes severe alkaline burns 1998, US PCC reported 6,000 cases, 95% accidental, 13% resulted in moderate to severe outcomes Ingestion of household solutions is usually accidental and occurs in young children, adult ingestions are usually suicide attempts

Alkalis, cont. Typical household ammonia contain 3-10% ammonia hydroxide pH less than 12.5 - caustic burns usually only seen with pH’s >12.5 so household products do not typically lead to significant burns patients present with oropharyngeal and epigastric pain may cause aspiration pneumonitis kids may bite smelling salts - 20% ammonia - can cause esophageal burns and mild respiratory symptoms

Alkalies, cont. Bleach - sodium hypochlorite - NaOCl taste terrible and spontaneously vomited never mix bleach with acid or alkaline cleaning agents - release of chlorine gas good to apply topically for any bites

Hydrocarbons

Hydrocarbons Organic compounds containing H and C Derived from plants or from petroleum distillates 3 basic types aliphatic aromatic halogenated Petroleum distillates - produced from fractional distillation of crude petroleum Terpenes - distillates of pinewood

Hydrocarbons, cont. Examples of petroleum distillates kerosene gasoline mineral spirits naphtha mineral seal oil diesel oil fuel oil

Hydrocarbons, cont. Characteristics surface tension - cohesiveness of molecules on the surface of a liquid volatility - tendency of a liquid to change into a gas or vapor viscosity - resistance of a substance to flow over a surface, directly relates to the aspiration hazard low verses high viscosity

Hydrocarbons, cont. Mechanism of Toxicity 64, 634 cases of HC exposure in 1994, as reported by the American Association of Poison Control Centers 24% required hospital treatment more than 1/2 of all exposures occur in children under the age of 6 years most exposures are accidental 22 people died in 1994

Hydrocarbons, cont. Mechanism of toxicity, cont. major threat is danger of aspiration pneumonitis vomiting increases the risk of aspiration when aspirated, petroleum distillates : inhibit surfactant - causing alveolar collapse and resultant hypoxemia cause bronchospasm and capillary damage cause hemorrhagic bronchitis cause pulmonary edema

Hydrocarbons, cont. Mechanism of toxicity, cont. Systemic toxicity can occur after oral ingestion CNS depression, GIT irritation, liver and kidney damage, cardiovascular toxicity

Hydrocarbons, cont. Characteristics of poisoning, 3 organ systems usually involved: Pulmonary, GI & CNS Signs and symptoms of pulmonary involvement coughing, gasping and choking smell of gasoline to the breath rales and wheezing upon auscultation hemoptysis and pulmonary edema

Hydrocarbons, cont. Signs and symptoms of GIT involvement irritation of oropharynx nausea and vomiting abdominal pain Signs and symptoms of CNS involvement cerebral hypoxemia lethargy somnolence coma or seizures

Hydrocarbons, cont. Management of poisoning To induce vomiting or not to induce vomiting Do not induce vomiting in patients who have ingested low viscosity petroleum distillate hydrocarbons ingestion as it increases the risk of aspiration pneumonitis Do Maintain airway and support respiration

Hydrocarbons, cont. Do induce vomiting in patients who have ingested: halogenated hydrocarbons insecticides turpentine aromatic hydrocarbons or ones which contain of heavy metals - must protect airway (endotracheal intubation)

Hydrocarbons, cont. Terpenes include pine oil, turpentine, and camphor pine oil - product of pine trees (Pine Sol) turpentine is a distillate from pine trees camphor - distillate of the camphor tree Have lower volatility and higher viscosity therefore less of a risk of aspiration than the petroleum distillates

Hydrocarbons, cont. Mechanism of Action of Turpentine and Pine oil Systemic toxicity results in GIT irritation and CNS depression see nausea, vomiting, diarrhea, weakness, somnolence, stupor and coma Treatment: GI tract decontamination - induce vomiting maintain airway transport

Hydrocarbons, cont. Camphor uses - OTC preparations such as local anesthetics, chest cold inhalants, etc. basically no therapeutic value, but still used problem occurs if it is ingested can cause CNS excitation and seizures, mechanism of action is unknown causes irritation of upper airway and mucous membranes Treatment - supportive care

Toxic Gases

Carbon Monoxide The most common form of poisoning From 1979 to 1988, 56,000 people died from CO Colorless, odorless, nonirritating gas Produced by incomplete combustion of carbon containing compounds Combines with Hb to form carboxyhemoglobin CO-Hb will not transport O2 T 1/2 of CO-Hb is 5-6 hours in room air, 90 min in pure O2 at 1 atm, 23 min in O2 at 3 atm

Carbon monoxide, cont. Sources: propane powered engines natural gas appliances - space heaters automobile exhaust gas log fireplaces kerosene heaters hibachi grills portable generators

Carbon monoxide, cont. Mechanism of action: Competes with O2 for active sites on Hb (220x the affinity for Hb as O2) Interference with cellular respiration at the mitochondria level, binds to cytochrome oxidase Induces smooth muscle relaxation Hypoxemia, tissue hypoxia, no cyanosis, CO-Hb is cherry red in color

Carbon monoxide, cont. Diagnosis based on patient presentation and a good history Signs and symptoms vary widely Signs depend on % CO-Hb levels in the blood Presence of cherry red blood is pathognomonic

Carbon monoxide, cont. Clinical grading of CO poisoning Mild headache, nausea, dizziness, vomiting, flu like symptoms Moderate confusion, slow thinking, shortness of breath, blurred vision, tachycardia, tachypnea, ataxia, weakness Severe chest pain, palpitations, severe drowsiness, disorientation, hypotension, syncope, myocardial ischemia, pulmonary edema

Carbon monoxide, cont. Exposure during pregnancy can be teratogenic Chronic low level exposure can cause: tiredness lethargy irritability visual impairment increased incidence of heart disease on atherosclerosis

Carbon monoxide, cont. Management of Toxicity: The antidote for CO poisoning is 100% oxygen hyperbaric chambers should be used more frequently than they currently are in the treatment of CO poisoning

Hydrogen sulfide poisoning Highly toxic, malodorous, intensely irritating gas Sources: decaying organic materials natural gas volcanic gas petroleum sulfur deposits sulfur springs Most exposures are occupational

Hydrogen sulfide, cont. Mechanism of action: inhibits mitochondrial cytochrome oxidase paralyzes the electron transport system inhibits cellular utilization of O2 metabolic acidosis secondary to anaerobic metabolism plenty of O2 in the bloodstream, cells can not utilize it, so no hypoxemia but tissue hypoxia

Hydrogen sulfide, cont. Mechanism of action, cont.: more potent cytochrome oxidase inhibitor than cyanide rapidly absorbed through the inhalation route metabolized by the liver and excreted through the kidneys cause of death is respiratory paralysis due to toxic effects of H2S on respiratory centers in the brain

Hydrogen sulfide, cont. Concentration (ppm) Clinical effect 0.02 odor threshold 100-150 nose/eye irritation, olfactory nerve paralysis 250-500 sore throat, cough, keratoconjunctivits, chest tightness, pulmonary edema 500-1000 headache, disorientation, loss of reasoning, coma, convulsions >1000 death

Hydrogen sulfide, cont. Treatment: rescuer protection basic life support give O2, hyperbaric oxygenation is beneficial nitrates are antidotal by inducing Meth-Hb - providing a large available source of ferric-heme which has a greater affinity for H2S than does cytochrome oxidase, sequestering sulfide ions freeing cytochrome oxidase

Cyanide Hydrocyanic acid, Prussic acid In 1994 only 360 cases of cyanide poisoning (300 were unintentional, 9 patients died) Sources: electroplating, jewelry and metal cleaners photographic processing fumigant rodenticide criminal tampering with OTC capsules Amygdalin - pits of peaches, cherries, apricots, apples, plums laetrile

Cyanide, cont. Mechanism of action: causes tissue hypoxia by binding with ferric iron of mitochondrial cytochrome oxidase, thus inhibiting the functioning of the electron transport chain and the cells ability to utilize O2 in oxidative phosphorylation substantial decrease in ATP production see a shift to anaerobic metabolism increased lactic acid production - metabolic acidosis

Cyanide, cont. Clinical presentation: tissue hypoxia, especially of the heart and brain (plenty of O2 in the bloodstream, cells can not utilize what is there) signs depend upon route and dose inhalation of cyanide gas usually produces rapid death delayed onset after exposure to Amygdalin

Cyanide, cont. Clinical presentations, cont. Patients who do not experience sudden collapse you will see anxiety, hyperventilation, CNS stimulation, tachycardia, palpitations Late signs of poisoning include nausea, vomiting, hypotension, generalized seizures, coma, apnea, a variety of cardiac dysrhythmias Smell of bitter almonds to the breath Absence of cyanosis

Cyanide, cont. Treatment: amyl nitrate - to induce Meth-Hb (same as with H2S) give O2

Heavy Metal Toxicity

Mechanism of Action Most common route of exposure is oral secondary is inhalation of fumes Toxicity is expressed biologically because of their ability to bind to one or more ligands of biologic enzyme systems which then inactivates the enzyme system

One of the few poisons that we have a chemical antidote for:

Chelating Agents Chemical antidotes - chemically inactivate the poison Compete with enzyme systems for the metals Reverse the metals toxic effects Enhance the excretion of the metal The chelate formed is a stable compound Chelates are water soluble Chelates are excreted by the kidneys

Chelating Agents, cont. How effective these chelating agents are depends upon: 1) the affinity of the chelator for the metal 2) distribution of the chelator to the parts of the body where the metal is 3) ability of the chelator to mobilize the metal from the body once the chelate is formed

Chelating Agents, cont. Properties of the ideal chelating agent: 1) greater affinity for the metal than for ligands of tissues 2) high water solubility 3) can penetrate into tissues 4) resistant to metabolic degradation by the body 5) forms a tight stable bond with the metal which is non toxic to the body

Chelating Agents, cont. Properties of the ideal chelating agent, cont. 6) be readily excreted unchanged 7) low affinity for calcium 8) minimal inherent toxicity 9) be absorbed readily when given orally

No drug has a single effect, drugs are two edged swords. Chelating Agents, cont. No drug has a single effect, drugs are two edged swords. Examples of a chelating agent: calcium disodium EDTA - can cause renal problems, fever, dermatitis, used to treat lead toxicity

Heavy Metals

Lead toxicity Sources - used in the past in medicines (sugar of lead), insecticides, pesticides, gasoline (tetraethyl lead), batteries, paints, manufacturing, automobile exhaust. The fall of the Roman empire was due to the fact they used lead for pipes to carry water and for drinking goblets and utensils.

Lead Toxicity, cont. Clinical features, plumbism: Acute intoxication: not common colic metallic taste to mouth vomiting, diarrhea or constipation increased thirst hemolysis, hemoglobinuria oliguria paresis and paresthesias

Lead Toxicity, cont. Chronic lead intoxication - much more common Burtonian line - dark gray bluish black line on the gingival margin (H2S + Pb = PbS) Basophilic stippling (clumping of RNA) Anemia Colic, diarrhea, vomiting Skeletal muscle weakness Increase uric acid in blood Headache, confusion, insomnia Lead palsy (wrist drop and foot drop)

Lead Toxicity, cont. Patient management: Acute intoxication - induce vomiting, give cathartics, give proteins to delay absorption (milk, egg whites), chelating agents Chronic toxicity - give chelating agents

Iron Toxicity Seen mostly in children, 40, 000 exposures/yr. Toxic doses: 20-60 mg/kg of elemental iron is potentially toxic 60-120 mg/kg is toxic but not usually fatal > 120 mg/kg is potentially fatal Only 10% of ingested iron is absorbed Most iron tablets contain 10-30% elemental iron by weight

Iron Toxicity, cont. Sources - dietary supplements Clinical features: toxicity develops when serum iron levels exceed the iron binding capacity of transferrin in the blood body is poorly equipped to handle excessive amounts of iron - can eliminate only very small amounts/day free iron damages tissues by direct corrosive effects, free iron is a potent vasodilators, directly injures blood vessels, causes hepatocellualr death, coagulation disturbances, and metabolic acidosis

Iron Toxicity, cont. Acute GI corrosive effects of iron, nausea, Clinical presentation of acute toxicity- 4 Stages Stage I - 30 min. to 6 hrs. post ingestion Acute GI corrosive effects of iron, nausea, abdominal pain, vomiting, and diarrhea, hematemesis, hematochezia and melena. Most patients with mild to moderate toxicity do not progress beyond this phase. Stage II - 6-24 hours post ingestion sometimes called the latent or quiescent period transient resolution of patient’s GI signs

Iron Toxicity, cont. Stage III - 12-48 hours post ingestion recurrence of GI hemorrhage, hematemesis, melena and bowel perforation may be seen acute circulatory shock, metabolic acidosis, respiratory distress syndrome death is common is this stage Stage IV - 4-6 weeks post ingestion gastric outlet obstruction or pyloric stenosis as a result of gastric scarring, vomiting

Iron Toxicity, cont. Chronic toxicity: Treatment: pigmented hepatic cirrhosis, diabetes mellitus, hyperpigmentation of the skin, hemosiderosis hemochromatosis Treatment: induce vomiting activated charcoal is of no value transport chelators

Mercury Toxicity Sources: Hg (Gr. - hydrargyros - water silver) drugs (antisyphilitic agents, diuretics, cathartics, topical salves), batteries, paint, shell fish, neon lamps, thermometers, industry (“mad as a hatter”), BP cuffs, wood preservatives, vaccines dental amalgam fillings (50% mercury, 35% silver, 13% tin, 2% copper with a trace of zinc)

Mercury Toxicity, cont. Exists in nature in 3 major forms: organic (methyl mercury) inorganic elemental Mechanism of Action: Forms covalent bonds with sulfide groups disrupting many important cellular functions

Mercury Toxicity, cont. Elemental mercury - quicksilver liquid at room temperature vaporizes easily at room temperature lung is major target organ due to inhalation of volatilized fumes lipid soluble and passes rapidly into blood stream see acute pulmonary symptoms, fever, chills, dyspnea, lethargy, confusion, vomiting

Mercury Toxicity, cont. Elemental mercury - quicksilver, cont. Chronic exposure - tremors, gingivitis, insomnia, shyness, memory loss, anorexia, depression ingestion is usually no problem - poor absorption from GIT

Mercury Toxicity, cont. Inorganic mercury - mercurial salts route of exposure - oral source - disc batteries, mercurous chloride, vaccines (0.01% thimerosal) clinical signs associated with the caustic effects signs and symptoms - pain, vomiting, hematemesis, renal failure

Mercury Toxicity, cont. Organic mercury: source - contaminated food products, methyl mercury contaminated seafood in the 1950’s in Japan killed over 1000 people (Minamata Bay) elevated levels found in blood stream of mothers and infants - source? (tuna) major signs and symptoms are neurological, visual field constriction, ataxia, paresthesia, hearing loss, muscle tremors, and even death

Mercury Toxicity, cont. Diagnosis is based on: Treatment: patient history and clinical signs urinary levels of mercury (values greater than 20-25 ug/L is abnormal) Treatment: acute therapy - same as any poison chronic - chelation therapy (BAL)

Arsenic Toxicity Commonly found throughout the earth’s crust, contaminates well water used in manufacture of herbicides and pesticides and computer chips tasteless and resembles sugar has been used as a therapeutic agent and as a poison for more than 2000 years most exposures are accidental and deaths are very rare

Arsenic Toxicity, cont. Mechanism of action: Inhibition of sulfhydryl group-containing cellular enzymes and the replacement of phosphate molecules in “high energy” compounds Trivalent arsenic is a carcinogen (lung and skin cancer) and is the most toxic form Toxic dose ranges from 1 mg to 10 grams Can be recovered from the hair, nails and skin

Arsenic Toxicity, cont. Clinical presentation: Acute exposure burning of the mouth and throat, nausea, vomiting, profuse diarrhea (rice water stool), garlic like odor to breath, increased capillary permeability, shock, renal damage

Arsenic Toxicity, cont. Chronic toxicity: skin pigmentation changes, palmar and plantar hyperkeratosis anorexia, GI symptoms anemia (see pale patient with areas of increased pigmentation and hyperemia - “Milk and Roses” complexion) Mee’s lines (white transverse bands in the nails) metallic taste to the mouth gangrene of the feet (“blackfoot disease”) encephalopathy

Arsenic Toxicity, cont. Diagnosis: Urine sample provide the most reliable diagnostic testing, >200ug/L are abnormal use of hair or nails is generally not useful in evaluating individual patients Treatment: supportive care and chelation therapy

Natural Chelators Chlorella (from algae) is a natural immune stimulant and has a high affinity for heavy metals (it contains sulfur bound amino acids and acts as a natural chelator) Garlic and cilantro (Chinese parsley) aid in the removal of heavy metals